What is the central dogma of molecular biology?

Central dogma of molecular biology

Frances Crick understood that the structure of DNA allowed it to ‘unzip’ to copy both strands of the molecule to make a new DNA molecule identical to the original one: this is called DNA replication and it is vital for DNA to function as the hereditary material.

DNA also controls what happens inside cells by controlling what proteins can be made. This is called protein synthesis and it occurs in 2 stages: transcription copies one strand of the DNA into an RNA molecule, which can be used as the instruction for ribosomes to make the right protein by translation.

What is a gene?

This is a difficult question to answer! But if we look at it simply, we could say that a gene is the stretch of DNA that is transcribed into RNA and then translated into protein.

How many genes do humans have in their DNA?

This is interesting – until recently we thought that humans had over a hundred thousand genes to give the instructions for all the proteins needed to make their cells and keep them alive. But the Human Genome Project showed us that we only have around 25,000 different genes – about the same number as a mouse!

Is all our DNA made of genes?

Actually, no, only a tiny percentage of all our DNA is made of genes. It might be hard to imagine, but if the DNA inside the nucleus of any cell in our body could be stretched out, it would measure 2 meters – that is as tall as a man! But the genes are only 3% of the total – that’s only 6 cm of our stretched out DNA. The genes are spread throughout the DNA.

What does the DNA which is not making genes do?

This is a much harder question! Since it is there, it must surely be doing something! Some parts may help genes work properly, other parts may help the DNA fold to make chromosomes, but the roles of most of the DNA which does not make proteins is so far unknown…plenty of Nobel Prize questions waiting to be answered in this area of research in the future!

How do the factors know where to start transcription?

In our bodies, and other eukaryotic organisms, the factors, which are protein molecules, gather together at the start of the gene using the sequence of DNA as a signal for where to begin.

Roger Kornberg won the Nobel Prize in 2006 for his work on how the transcription factors, enzymes and parts of the DNA interact to control how transcription occurs in the nuclei of cells.

Which molecules make the RNA during transcription?

Enzymes (which are usually proteins) are molecules that do almost everything inside cells, so it is not surprising that it is an enzyme which joins nucleotides together to make the polymer RNA during transcription – its name is RNA polymerase.

How are the different kinds of RNA made?

Transcription makes the RNA copy of the gene which will leave the nucleus to be translated into a protein in the cytoplasm – this is called messenger RNA, or mRNA. Other RNA molecules help to make proteins by bringing amino acids to ribosomes – they are transfer RNA, or tRNA, and the ribosomes themselves are made from protein and a third kind of RNA known as ribosomal RNA, rRNA. All RNA molecules (mRNA, tRNA and rRNA) are made by transcription in the nucleus.

But RNA is not simply an intermediate molecule between DNA and protein... Tom Cech won a Nobel Prize in Chemistry in 1989 for showing that RNA can catalyse reactions inside cells - you can choose questions to ask him in the MoleClues Nobel Room.

Can RNA molecules control which proteins are made in a cell?

Yes, and in exciting ways that we are only just starting to understand!How long the mRNA can survive out in the hostile environment of the cytoplasm is one way that determines how much of its protein can be made, so the “half life” (time taken for half of the molecules to be degraded) of mRNA is important, as well as how much of it is made and when during the life of a cell.

Recently (2006) another Nobel Prize in Physiology was awarded to Andrew Z. Fire and Craig C. Mello for the discovery of how mRNA can be degraded in the cytoplasm when it occurs in double-stranded pairs; this is called RNA interference, and it effectively shuts off the information from the gene. This can occur when the two complementary mRNA molecules from opposite strands of DNA come together. In addition, tiny (21-23 nucleotides long) microRNA molecules can also stick to normal mRNA to slow down or even stop the protein being made. These discoveries show the importance of RNA molecules in regulating the activity of genes and opens up possibilities for designing RNA molecules as medicines to ‘silence’ genes which are overactive and cause disease.

If we have the same number of genes as a mouse, do we also have the same number of proteins in our cells?

No, we have many, many more! That is how we can be bigger and more complex than a mouse! We are just starting to identify all the proteins that can be made by human cells, in the Human Proteome Project. We already know some ways that human genes can make similar, but very slightly different proteins from a piece of DNA by having some alternative pieces for short sections of the gene. These alternative regions are separated by short sequences of DNA called introns, which are copied into RNA during transcription, but are cut out before the mRNA leaves the nucleus. One difference between our DNA and the DNA found in a mouse cell is that our cells’ genes have many more introns.

Is protein synthesis important in Evolution?

Yes! The ability to make different proteins, even if they are just slight variations on existing proteins, may help cells survive in an ever-changing environment, which increases the survival chances for the whole organism, whose genes can then be passed to the next generation. The ability to “watch” where and when particular proteins are made inside cells of different organisms is now possible by tagging them with fluorescent molecules.

How can studying protein synthesis contribute to medicine?

Many aspects of protein synthesis have implications for understanding how normal cells control which proteins are made at which time during development, and what happens if their production or structure changes in diseased tissues, especially in cancer, heart diseases and metabolic diseases including those causing inflammation. Designing RNA molecules to silence faulty genes is one way. Understanding transcription will also help us to understand how stem cells can give rise to all the different cells of the body and how they might be used in therapeutic techniques.For the discovery and development of the green fluorescent protein, GFP, to study protein synthesis, Osamu Shimomura, Martin Chalfie and Roger Y. Tsien, were awarded the Nobel Prize in Chemistry in 2008. Watch our video about the Prize